One of the characteristics of vector administration into the CNS is the ability of the transgene products and/or viral particles to travel along neural pathways. In our preliminary experiments in monkeys where the AAV-2 vector was administered into the striatum, transgene product was detected in afferent and efferent regions including the internal and external portion of the globus pallidus, subthalamic nucleus, substantia nigra reticulata and compacta, thalamus and cortex at 3 or 8 weeks after gene delivery. This strongly indicates that both retrograde and anterograde transport of vector and transgene product must be carefully evaluated as it may impact therapeutic applications of gene transfer. As the PDGTSG has identified rAAV and lentviral vectors as the initial two most promising vectors (see Principal Projects I and II) these will be the focus of this Pipeline Project. To address this transport issue this project will systematically analyze the axonal transport characteristics of AAV-2, the alternative serotype AAV-5 and lentiviral vectors in monkeys following intrastriatal administration. Each vector type will be delivered unilaterally into the striatum of normal monkeys and resulting gene expression and presence of the gene product will be detected at the site of gene delivery and projection sites. Fuorophore-labelled viral particles will be delivered in the contralateral striatum and detected at 48 hours later at the injection site and the projection regions. Results of this project will lead to an understanding of patterns of distribution of each of the viral vectors and will provide critical information regarding final design of Principal Projects.